FDA Approvals in RCC and Chronic ITP, 2018 ELCC Highlights, and More

Gina Columbus

Published: Friday, Apr 20, 2018

Today-

FDA approvals in renal cell carcinoma and chronic immune thrombocytopenia, an FDA initiative to streamline development processes, disappointing findings in a kidney cancer trial, and highlights from the 2018 European Lung Cancer Congress.

Welcome to OncLive News Network! I’m Gina Columbus.

The FDA has approved the combination of nivolumab and ipilimumab as a frontline treatment for intermediate- and poor-risk patients with advanced renal cell carcinoma.

The approval is based on results from the randomized phase III CheckMate-214 trial, which showed that frontline treatment with the combination of nivolumab and ipilimumab reduced the risk of death by 32% versus sunitinib for patients with metastatic RCC. The risk reduction was 37% in patients with intermediate- and poor-risk RCC, which made up 75% of the intent-to-treat population.

Moreover, the median overall survival in the overall population was not reached with the combination versus 32.9 months with sunitinib. In those patients with intermediate- and poor-risk RCC, the median OS was not reached with the combination and was 26.0 months in the sunitinib arm. There was not a benefit for the combination versus sunitinib in those with favorable risk.

Across the full ITT population, the median PFS was not improved, and the PFS in the intermediate- and poor-risk group was 11.6 months with the combination versus 8.4 months with sunitinib.

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In chronic immune thrombocytopenia, the FDA has approved the SYK inhibitor fostamatinib, known by the trade name Tavalisse, as a second-line treatment for patients following insufficient response to a previous therapy.

The decision was based on findings from 2 randomized trials and 1 open-label extension study.

In the first randomized study, known as FIT-1, 18% of patients treated with fostamatinib experienced a platelet response versus none in the placebo arm. The second study, known as FIT-2, showed that a stable platelet response was seen in 16% of patients in the fostamatinib group compared with 4% treated with placebo.

Patients from these trials could also be included in an open-label expansion cohort, known as FIT-3, in which 23% of those who received prior placebo in FIT-1 or -2 had a platelet response to fostamatinib.

With the increase in platelet counts across studies, there were fewer cases of bleeding experienced by patients in the fostamatinib arm compared with placebo at 29% versus 37%, respectively.

Rigel Pharmaceuticals, the manufacturer of fostamatinib, plans to have the agent ready for commercial launch in late May 2018.

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The FDA has announced plans to ease the development of genetic and genomic-based tests and introduced guidelines designed to accelerate the submission process for investigational cancer drugs and biological products.

The agency stated that it had finalized guidances intended to spur efficient development of a novel technology that scans a person’s DNA to diagnose genetic diseases and guide medical treatments.

The first is titled Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics, and allows test developers to rely on clinical evidence from FDA-recognized public databases to support clinical claims for their tests. It will also help provide assurance of the accurate clinical evaluation of genomic test results.

The agency said that using FDA-recognized databases will provide test developers with an efficient path for marketing clearance or approval of a new test.

The second guidance is titled Considerations for Design, Development, and Analytical Validation of Next Generation Sequencing–Based In Vitro Diagnostics Intended to Aid in the Diagnosis of Suspected Germline Diseases. This provides recommendations for designing, developing, and validating the NGS-based tests used to diagnose individuals with suspected genetic diseases.

In renal cell carcinoma, phase III data showed that adjuvant treatment with axitinib did not extend disease-free survival versus placebo for patients at high risk of recurrent disease after nephrectomy.

The findings, which were from the phase III ATLAS trial, showed that the study missed the primary DFS endpoint. Pfizer, the manufacturer of the VEGFR tyrosine kinase inhibitor, stated that an independent data monitoring panel recommended stopping the trial. The company announced that detailed results from the study will be presented at an upcoming medical meeting.

The global, multicenter, double-blind phase III study randomized 724 patients at high risk for RCC recurrence after nephrectomy to either adjuvant axitinib at 5 mg twice daily or placebo. Patients received treatment for 1 to 3 years.

In its statement, Pfizer noted that there were no new safety signals, with adverse events similar to previously reported results with axitinib.

Another VEGFR TKI, sunitinib, previously demonstrated success in this setting and was approved by the FDA in November 2017.

************************************

The 2018 European Lung Cancer Congress took place in Geneva, Switzerland last week, highlighting the most recent data within the lung cancer landscape.

In 3-year survival findings from the phase II POPLAR study that were presented at the meeting, anti PD-L1 immunotherapy with atezolizumab was found to be strongly superior to docetaxel in locally advanced or metastatic non–small cell lung cancer.

Investigators explained that the results were not specific to PD-L1 expression, which means the search must continue for biomarkers to improve targeting with this drug.

OS was significantly higher with atezolizumab at 2 and 3 years compared with docetaxel. Investigators said 32.2% of patients in the atezolizumab arm were alive at 2 years compared with 16.6% in the docetaxel cohort. At 3 years, 18.7% of patients on atezolizumab were alive versus 10% in the docetaxel group. Moreover, the long-term OS benefit with atezolizumab was observed in both squamous and non-squamous histologies and occurred regardless of PD-L1 expression level.

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An analysis of the phase III FLAURA study, which was also presented at the meeting, showed that first-line treatment with osimertinib led to a clinically meaningful delay in time from randomization to progression on subsequent treatment or death versus standard of care EGFR tyrosine kinase inhibitors, establishing the agent as a new standard of care in the frontline setting for patients with EGFR-mutant non–small cell lung cancer.

The most common second-line therapy in the osimertinib arm was platinum-based chemotherapy, whereas patients in the standard-of-care arm most frequently received subsequent osimertinib. The median PFS2 was not reached for patients receiving frontline osimertinib compared with 20.0 months in patients receiving standard-of-care. This was equivalent to a 42% reduction in the risk of progression on second-line therapy or death.

These data add to the pivotal findings from the FLAURA study that were published in 2017, in which the median progression-free survival with osimertinib was 18.9 months versus 10.2 months for standard-of-care. Additionally, a nonstatistically significant improvement in overall survival was observed with osimertinib compared with standard-of-care.

Based on data from the FLAURA trial, the FDA is currently considering approval for osimertinib as a frontline therapy for EGFR-mutant NSCLC.

*****************************************

This week, we sat down with Dr Bradley Monk, of Arizona Oncology, to discuss the FDA approval of rucaparib as a maintenance therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.

SELECTEDLANGUAGE

Today-

FDA approvals in renal cell carcinoma and chronic immune thrombocytopenia, an FDA initiative to streamline development processes, disappointing findings in a kidney cancer trial, and highlights from the 2018 European Lung Cancer Congress.

Welcome to OncLive News Network! I’m Gina Columbus.

The FDA has approved the combination of nivolumab and ipilimumab as a frontline treatment for intermediate- and poor-risk patients with advanced renal cell carcinoma.

The approval is based on results from the randomized phase III CheckMate-214 trial, which showed that frontline treatment with the combination of nivolumab and ipilimumab reduced the risk of death by 32% versus sunitinib for patients with metastatic RCC. The risk reduction was 37% in patients with intermediate- and poor-risk RCC, which made up 75% of the intent-to-treat population.

Moreover, the median overall survival in the overall population was not reached with the combination versus 32.9 months with sunitinib. In those patients with intermediate- and poor-risk RCC, the median OS was not reached with the combination and was 26.0 months in the sunitinib arm. There was not a benefit for the combination versus sunitinib in those with favorable risk.

Across the full ITT population, the median PFS was not improved, and the PFS in the intermediate- and poor-risk group was 11.6 months with the combination versus 8.4 months with sunitinib.

*********************************

In chronic immune thrombocytopenia, the FDA has approved the SYK inhibitor fostamatinib, known by the trade name Tavalisse, as a second-line treatment for patients following insufficient response to a previous therapy.

The decision was based on findings from 2 randomized trials and 1 open-label extension study.

In the first randomized study, known as FIT-1, 18% of patients treated with fostamatinib experienced a platelet response versus none in the placebo arm. The second study, known as FIT-2, showed that a stable platelet response was seen in 16% of patients in the fostamatinib group compared with 4% treated with placebo.

Patients from these trials could also be included in an open-label expansion cohort, known as FIT-3, in which 23% of those who received prior placebo in FIT-1 or -2 had a platelet response to fostamatinib.

With the increase in platelet counts across studies, there were fewer cases of bleeding experienced by patients in the fostamatinib arm compared with placebo at 29% versus 37%, respectively.

Rigel Pharmaceuticals, the manufacturer of fostamatinib, plans to have the agent ready for commercial launch in late May 2018.

*********************************

The FDA has announced plans to ease the development of genetic and genomic-based tests and introduced guidelines designed to accelerate the submission process for investigational cancer drugs and biological products.

The agency stated that it had finalized guidances intended to spur efficient development of a novel technology that scans a person’s DNA to diagnose genetic diseases and guide medical treatments.

The first is titled Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics, and allows test developers to rely on clinical evidence from FDA-recognized public databases to support clinical claims for their tests. It will also help provide assurance of the accurate clinical evaluation of genomic test results.

The agency said that using FDA-recognized databases will provide test developers with an efficient path for marketing clearance or approval of a new test.

The second guidance is titled Considerations for Design, Development, and Analytical Validation of Next Generation Sequencing–Based In Vitro Diagnostics Intended to Aid in the Diagnosis of Suspected Germline Diseases. This provides recommendations for designing, developing, and validating the NGS-based tests used to diagnose individuals with suspected genetic diseases.

In renal cell carcinoma, phase III data showed that adjuvant treatment with axitinib did not extend disease-free survival versus placebo for patients at high risk of recurrent disease after nephrectomy.

The findings, which were from the phase III ATLAS trial, showed that the study missed the primary DFS endpoint. Pfizer, the manufacturer of the VEGFR tyrosine kinase inhibitor, stated that an independent data monitoring panel recommended stopping the trial. The company announced that detailed results from the study will be presented at an upcoming medical meeting.

The global, multicenter, double-blind phase III study randomized 724 patients at high risk for RCC recurrence after nephrectomy to either adjuvant axitinib at 5 mg twice daily or placebo. Patients received treatment for 1 to 3 years.

In its statement, Pfizer noted that there were no new safety signals, with adverse events similar to previously reported results with axitinib.

Another VEGFR TKI, sunitinib, previously demonstrated success in this setting and was approved by the FDA in November 2017.

************************************

The 2018 European Lung Cancer Congress took place in Geneva, Switzerland last week, highlighting the most recent data within the lung cancer landscape.

In 3-year survival findings from the phase II POPLAR study that were presented at the meeting, anti PD-L1 immunotherapy with atezolizumab was found to be strongly superior to docetaxel in locally advanced or metastatic non–small cell lung cancer.

Investigators explained that the results were not specific to PD-L1 expression, which means the search must continue for biomarkers to improve targeting with this drug.

OS was significantly higher with atezolizumab at 2 and 3 years compared with docetaxel. Investigators said 32.2% of patients in the atezolizumab arm were alive at 2 years compared with 16.6% in the docetaxel cohort. At 3 years, 18.7% of patients on atezolizumab were alive versus 10% in the docetaxel group. Moreover, the long-term OS benefit with atezolizumab was observed in both squamous and non-squamous histologies and occurred regardless of PD-L1 expression level.

*****************************************

An analysis of the phase III FLAURA study, which was also presented at the meeting, showed that first-line treatment with osimertinib led to a clinically meaningful delay in time from randomization to progression on subsequent treatment or death versus standard of care EGFR tyrosine kinase inhibitors, establishing the agent as a new standard of care in the frontline setting for patients with EGFR-mutant non–small cell lung cancer.

The most common second-line therapy in the osimertinib arm was platinum-based chemotherapy, whereas patients in the standard-of-care arm most frequently received subsequent osimertinib. The median PFS2 was not reached for patients receiving frontline osimertinib compared with 20.0 months in patients receiving standard-of-care. This was equivalent to a 42% reduction in the risk of progression on second-line therapy or death.

These data add to the pivotal findings from the FLAURA study that were published in 2017, in which the median progression-free survival with osimertinib was 18.9 months versus 10.2 months for standard-of-care. Additionally, a nonstatistically significant improvement in overall survival was observed with osimertinib compared with standard-of-care.

Based on data from the FLAURA trial, the FDA is currently considering approval for osimertinib as a frontline therapy for EGFR-mutant NSCLC.

*****************************************

This week, we sat down with Dr Bradley Monk, of Arizona Oncology, to discuss the FDA approval of rucaparib as a maintenance therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.